Individuals infected with HIV are susceptible to a wide range of opportunistic fungal infections. Available drugs to treat the major fungal pathogens are limited due to toxicity and other adverse reactions frequently occurring in people with AIDS. We propose a comprehensive team effort for the discovery of novel drug targets in Candida albicans that is likely to lead to the discovery of agents effective against pathogenic fungi. Three separate but interdependent projects are proposed. Core service units and MycoPharmaceuticals, Inc., a new biotechnology company, will provide reagents and test systems for use by the projects. The Project by Fink will characterize the activities of C. albicans genes controlling dimorphic switching. The elucidation of the dimorphism pathway at the molecular level is likely to reveal targets for development of drugs that will limit the pathogenic potential of this organism. The project by Koltin) will study the mode of action of CaMDR, a C. albican multiple drug resistant protein whose gene was recently cloned in Dr. Koltin's laboratory. Searchers to bypass the resistance mechanism by molecular approaches could identify novel ways to combat disease. The project by Robins will study the molecular biology of chitin biosynthesis in C. albicans. By understanding the relationship between chitin content and pathogenicity, essential cellular targets for drug design will be identified.